Cinética celular em lesöes pré-invasivas e invasivas do epitélio escamoso cervical: estudo morfológico e imunoistoquímico / Cellular kinetics in preinvasive and invasive lesions of cervical squamous epithelium: morphologic and immunohistochemical study

RESUMO

Avaliar quantitativamente a apoptose (morte celular programada) e a taxa de proliferaçäo celular no espectro das lesöes neoplásicas do colo uterino. Materiais e Métodos: Analisamos 81 biópsias cervicais previamente diagnosticadas na Divisäo de Patologia do Instituto Adolfo Lutz segundo a classificaçäo da OMS como sendo neoplasia intraepitelial cervical de grau 1 NIC 1=20,NIC2=19,NIC3=23 e carcinoma de células escamosas (CCE)=19. Foi utilizado o método imunoistoquímico para detecçäo das células em proliferaçäo (MIB-1) e o método de TUNEL para a apoptose. As células foram contadas através de fotomicrografia digital, sendo que o número variou de 83 a 2975 média=1515,62) para MIB-1 e 315 a 3565 para apoptose (média=1273,24). Resultados: Houve um aumento progressivo nas taxas de proliferaçäo (por cento) com a severidade da lesäo (NIC 1=22,7;NIC 2=34,5;NIC 3=38,3;CCE=52,6P<0,0001). O mesmo foi obtido com as taxas de apoptose (por cento) (NIC 1=0,30;NIC 2=0,55;NIC 3=0,70;CCE=1,19p<0,0001) e o índice de renovaçäo celular (por cento) (NIC 1=23,0;NIC 2=35,0;NIC 3=39,0;CCE=53,8p<0,0001). Surpreendentemente a razäo das taxas proliferaçäo/ apoptose näo mostrou aumento progressivo (NIC 1=75,6;NIC 2=62,7;NIC 3=54,7; CCE=44,2). Conclusäo: Observamos aumento paralelo tanto nas taxas de proliferaçäo como nas de apoptose com o grau das lesöes cervicais. As taxas crescentes de apoptose possivelmente representam a persistência de alguns mecanismos compensatórios de regulaçäo da populaçäo celular

ABSTRACT

To assess proliferative and apoptotic rates in squamous lesions of the uterine cervix. Materialand Methods: 81 cervical biopsies were classified as cervical intraepithelial neoplasia grade 1 CIN1 = 20,CIN2 = 19, CIN3 = 23 and squamous cell carcinoma (SCC) = 19, according to WHO classification. Histologicalsections were submitted to MIB-1 immunostaining by streptavidin-peroxidase amplification. In situ end-labeling of DNA strand breaks by TUNEL method was used to enhance the detection of apoptosis. Allcells representative of the pertinent lesion were counted in each sample in digital hotomicrographs andthe results were expressed as positive cells %. The groups were compared using a one-way analysis ofvariance (ANOVA). Statistical significance was defined as a P< 0.05. Results: There was progressiveincrease of proliferation rate (%) with the severity of lesion CIN 1 = 22.7; CIN 2 = 34.5; CIN 3 = 38.3; SCC =52.6 p<0.0001). The same was obtained with apoptotic rate (%) (CIN 1 = 0.30; CIN 2 = 0.55; CIN 3 = 0.70;SCC = 1.19 p<0.0001), and turnover rate (%) (CIN 1 = 23.0; CIN 2 = 35.0; CIN 3 = 39.0; SCC = 53.8 p<0.0001).Surprisingly, the ratio of proliferation/apoptotic rate did not show a progressive increase (CIN 1 = 75.6;CIN 2 = 62.7; CIN 3 = 54.7; SCC = 44.2). Conclusions: There is an increase in both proliferation andapoptosis with increasing atypical in cervical lesions. Increase in apoptotic rate possibly representspersistence of some compensatory regulation mechanisms of cell population